When synthetic or natural materials, such as those used in implants and tissue engineering, come in contact with living systems, they induce specific or general responses in cells and the extracellular matrix. Cells are known to respond to both the chemistry and the mechanical properties of the surface to which they adhere. This project will explore new thin films for regulating cell adhesion and controlling cell behavior. In this work, protein and cell adhesion to ultrathin films made by the polyelectrolyte multilayering technique will be investigated. The study involves the synthesis of new polymers, their assembly, and a coordinated evaluation of the response of cells to these synthetic materials. Functional groups will be introduced into the polymers to control hydrophilicity and crosslinking. Distinction will be made between the nonspecific chemistry presented to the extracellular matrix at the surface of the film, and the film interior, which will impact the mechanical properties. The purpose of this distinction is to separate contributions of nonspecific protein adsorption and film modulus-induced cellular responses to cell adhesion, differentiation, and proliferation. The three interleaving groups of Aims present increasing levels of feedback with biological systems. We start with a goal of producing a minimally adhesive background surface, then we "dope" it with precise levels of adhesion-promoting protein. We continue with an eye towards controlled chemical and physical interactions between cells and substrates. Driven partly by hypothesis and partly by a quest for new materials at the biointerface, we are interested in how cellular organization responds to broad chemical and physical cues. Points of novelty include new materials compositions, migration of a promising technology to the biointerface, methods of crosslinking, and forming gradients in mechanical properties in the plane of the film.